The present invention relates to the use of acylated amino acid ester derivatives as a new class of edible, preferably partially digestible, fat mimetics.
Many foods which provide gustatory satisfaction contain significant fat levels, yet fats provide nine calories per gram compared to four calories per gram provided by protein and carbohydrates. Dietary fats represent approximately 40 to 45% of the U.S. daily caloric intake, significantly more than England, which has the same daily food consumption, and the percentage has risen since 1936 (Merten, H. L., J. Agr. Food Chem. (1970) 18, 1002-1004). A large number of national advisory committees on nutrition have made recommendations differing in detail, but the common theme is a reduction in the total amount of fat in our diet for medical and health reasons, for both individuals who desire a caloric reduction and those who do not (Gottenbos, J. J., chapter 8 in Beare-Rogers, J., ed., Dietary Fat Requirements in Health and Development, A.O.C.S. 1988, page 109). Hence, major research efforts have focused on ways to produce food substances that provide the same functional and organoleptic properties as fats, but not the calories.
A major strategy for developing low calorie replacement fats has been to structurally re-engineer natural triglycerides in such a way as to retain their conventional functional properties in foods, while removing their susceptibility toward hydrolysis or subsequent absorption during digestion. To this end, the the fatty acids attached to glycerol have been replaced with alternate acids (U.S. Pat. No. 3,579,548 to Whyte); groups have been inserted between the fatty acids and the glycerol backbone (e.g., ethoxy or propoxy groups, U.S. Pat. No. 4,861,613 to White and Pollard); the ester linkages have been replaced by ether linkages (U.S. Pat. No. 3,818,089 to Bayley and Carlson, and Can. Pat. No. 1,106,681 to Trost); the ester linkages have been reversed (U.S. Pat. No. 4,508,746 to Hamm); and the glycerol moeity has been replaced with an alternate alcohol (e.g., ethylene glycol in U.S. Pat. No. 2,924,528 to Barskey et al., and U.S. Pat. No. 2,993,063 to Alsop and Carr).
A second major approach to the development of a low calorie fat replacement has been to explore or synthesize nonabsorbable polymeric materials structurally unlike triglycerides, but having physical properties similar to edible fat. Mineral oil was disclosed as early as 1894 (U.S. Pat. No. 519,980 to Winter), and, more recently, polydextrose (U.S. Pat. No. 4,631,196 to Zeller), polyglucose and polymaltose (U.S. Pat. No. 3,876,794 to Rennhard), polysiloxane (Eur. Pat. Ap. No. 205,273 to Frye), jojoba wax (W. Ger. Pat. No. 3,529,564 to Anika), polyethylene polymers (E. Ger. Pat. No. 207,070 to Mieth, et al.), polyoxyalkylene esters (U.S. Pat. No. 4,849,242 to Kershner), polyvinyl alcohol esters (U.S. Pat. No. 4,915,974 to D'Amelia and Jacklin), and polymerized C.sub.18 fatty acid ethyl esters (U.S. Pat. No. 4,980,191 to Christensen) have been suggested.
A third major strategy combines the first two. Rather than restructure triglyceride molecules or find a substitute structurally very dissimilar, this approach explores the use of various polyol esters, compounds which have numbers of fatty acid groups in excess of the three in conventional fat triglycerides, as nonabsorbable fat replacements. Fully esterified sugar alcohols were suggested as fat replacements during World War I (notably mannitol, Lapworth, A., and Pearson, L. K., and Halliburton, W. D., et al., J. Biol. Chem. (1919) 13, 296-300 and 13, 301-305); Minich suggested esterifying pentaerythritol, a tetrahydric neopentyl sugar alcohol which can be formed from pentaerythrose, in 1960 (U.S. Pat. No. 2,962,419); and the Southern and Western Regional Research Laboratories of the U.S.D.A. investigated the feasibility of using amylose esters as new-type fats during the 1960's (see Booth, A. N., and Gros, A. T., J. Amer. Oil Chem. Soc. (1963) 40, 551-553 and the references cited therein). More recently, sucrose polyesters (U.S. Pat. No. 3,600,186 to Mattson and Volpenhein) and other acylated sugars (U.S. Pat. No. 4,840,815 to Meyer, et al.) have been suggested. The caloric availability and digestibility of a series of dimeric and polymeric glycerides including diglyceride esters of succinic, fumaric, and adipic acids, and polymeric fats from stearic, oleic and short-chain dibasic acids were assessed by the U.S.D.A. group cited supra, and polyglycerol esters have since been suggested (U.S. Pat. No. 3,637,774 to Babayan and Lehman).
Nondigestible or nonabsorbable edible fat replacements have proved disappointing when tested in feeding trials, where gastrointestinal side effects occurred, in some cases so extreme that frank anal leakage was observed (for recent reviews, see Hamm, D. J., J. Food Sci. (1984) 49, 419-428, Haumann, B. J., J. Amer. Oil Chem. Soc. (1986) 63, 278-288, and LaBarge, R. G., Food Tech. (1988) 42, 84-89). Nondigestible fats appear to act as a laxative and are expelled from the body, eliciting foreign body reactions like those early documented for mineral oil (Stryker, W. A., Arch. Path. (1941) 31, 670-692, more recently summarized in Goodman and Gilman's Pharmacological Basis of Therapeutics, 7th ed., Macmillan Pub. Co., N.Y. 1985, pp. 1002-1003). In the U.S.D.A.,s assessment of the caloric availability and digestibility of a series of new-type fats in the 1960's (e.g., amylose fatty acid esters, diglyceride esters of succinic, fumaric, and adipic acids, and polymeric fats from stearic, oleic and short-chain dibasic acids; see Booth, A. N., and Gros, A. T., cited above), rats fed the experimental fats exhibited undesirable gastrointestinal side effects similar to what had already been observed with mineral oil consumption by people. In several of the balance studies, the diarrhea was so extreme that digestibility coefficients could not be calculated in the trial feedings (ibid., Table l, p. 552).
Polyglycerol and polyglycerol esters, suggested as fat replacements by Babayan and Lehman (cited above), have been suggested for use as fecal softening agents as well (U.S. Pat. No. 3,495,010 to Fossel). A number of remedies have been recommended to combat the anal leakage observed when sucrose polyesters are ingested (e.g., employing cocoa butters, U.S. Pat. No. 4,005,195 to Jandacek, incorporating saturated fatty groups, Eur. Pat. Ap. No. 233,856 to Bernhardt, or mixing residues, U.S. Pat. No. 4,797,300 to Jandacek, et al.). Saturated fatty acids have been disclosed as anti-anal leakage agents for polyorganosiloxane fat substitutes (U.S. Pat. No. 4,925,692 to Ryan), and dietary fiber preparations have been incorporated into foodstuffs containing other fat replacements to help inhibit the diarrheal effect (U.S. Pat. No. 4,304,768 to Staub et al. and Eur. Pat. Ap. No. 375,031 to DeBoer and Kivits). Partially digestible fat replacements have also been suggested (U.S. Pat. No. 4,830,787 to Klemann and Finley; U.S. Pat. No. 4,849,242, cited above; and U.S. Pat. No. 4,927,659 to Klemann, et al.).